Background:The emergence of new SARS-CoV-2 has promoted the development of new serological tests that could be complementary to RT-PCR. Nevertheless, the assessment of clinical performances of available tests is urgently required as their use has just been initiated for diagnose. Objectives: The aim of this study was to assess the performance of three immunoassays for the detection of SARS-CoV-2 antibodies. Methods: Two automated immunoassays (Abbott SARS-CoV-2 CLIA IgG and Euroimmun Anti-SARS-CoV-2 ELISA IgG/IgA assays) and one lateral flow immunoassay (LFIA NG-Test® IgG-IgM COVID-19) were tested. 293 specimens were analyzed from patients with a positive RT-PCR response, from patients with symptoms consistent with COVID-19 but exhibiting a negative response to the RT-PCR detection test, and from control group specimens. Days since symptoms onset were collected from clinical information sheet associated with respiratory tract samples. Results: Overall sensitivity for IgG was equivalent (around 80 %) for CLIA, ELISA and LFIA. Sensitivity for IgG detection, > 14 days after onset of symptoms, was 100.0 % for all assays. Overall specificity for IgG was greater for CLIA and LFIA (more than 98 %) compared to ELISA (95.8 %). Specificity was significantly different between IgA ELISA (78.9 %) and IgM LFIA (95.8 %) (p < 0.05). The best agreement was observed between CLIA and LFIA assays (97 %; k = 0.936). Conclusion: Excellent sensitivity for IgG detection was obtained > 14 days after onset of symptoms for all immunoassays. Specificity was also excellent for IgG CLIA and IgG LFIA. Our study shows that NG-Test® is reliable and accurate for routine use in clinical laboratories. BackgroundA new acute respiratory syndrome named coronavirus disease 2019 (COVID-19) has emerged from the region of Wuhan in China in December 2019. This infection, widespread all over the world, is caused by a novel Sarbecovirus designated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), associated with severe morbidity and mortality [1][2][3]. The detection of viral RNA by real time reverse transcriptase-Polymerase chain reaction (RT-PCR) in respiratory tract samples is considered as the gold standard method for screening and

Summary Classical activation of macrophages (M(LPS+IFNγ)) elicits the expression of inducible nitric oxide synthase (iNOS), generating large amounts of NO and inhibiting mitochondrial respiration. Upregulation of glycolysis and a disrupted tricarboxylic acid (TCA) cycle underpin this switch to a pro-inflammatory phenotype. We show that the NOS cofactor tetrahydrobiopterin (BH 4 ) modulates IL-1β production and key aspects of metabolic remodeling in activated murine macrophages via NO production. Using two complementary genetic models, we reveal that NO modulates levels of the essential TCA cycle metabolites citrate and succinate, as well as the inflammatory mediator itaconate. Furthermore, NO regulates macrophage respiratory function via changes in the abundance of critical N-module subunits in Complex I. However, NO-deficient cells can still upregulate glycolysis despite changes in the abundance of glycolytic intermediates and proteins involved in glucose metabolism. Our findings reveal a fundamental role for iNOS-derived NO in regulating metabolic remodeling and cytokine production in the pro-inflammatory macrophage.

Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

1. The defence mechanisms of the body are predominantly functions of the reticulo-endothelial system (RES). Stimulation of the RES leads to increased body defence indicated by increased phagocytic activity, raised serum \g=g\-globulin and increased protection of experimental animals against virulent infections. The strongest RES stimulants appear to be oestrogens, natural and synthetic.2. In the mouse, 0\m=.\002 mg. diethylstilboestrol daily is sufficient to produce significant prolongation of survival time against infection.3. RES activity varies at different stages of the oestrous cycle and of pregnancy in both the rat and the mouse. The stages where the activity is greatest correspond with those in the human subject when the output of oestrogens is increased.4. The results suggest that oestrogen is the natural stimulant of body defence in both the male and female, the latter having high oestrogen levels when protection against infection is normally most needed. 5. RES stimulation does not rise in step with oestrogenicity, and oestrogenic compounds have two separate biological activities\p=m-\onewhich stimulates the RES to raise body defence, and one which acts on the reproductive organs; these two activities are apparently unrelated, although shared by the same molecule.